Acinic Cell Carcinoma

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Hematol Oncol Stem Cell Ther 2(1) First Quarter 2009 hemoncstem.edmgr.com 259

According to The World Health Organization, acinic cell carcinoma (ACC) is a malignant epittthelial neoplasm of the salivary glands in which

at least some of the neoplastic cells demonstrate serous acinar cell differentiation characterized by cytoplasmic zymogen secretory granules. Salivary ductal cells can also be a component of this lowtgrade neoplasm that most often occurs in the parotid gland and presents at a relatively younger age than other salivary gland tumors. This malignant disease shows a female predilection.1

ACC was referred to as an entity for the first time more than 50 years ago by Godwin et al.2 The terms “acinar” and “serous” refer to the histologic resemttblance of tumor cells to the secretory parenchymatous cells of the parotid, grouped in grapetlike clusters and hence given the latin name “acinus” (Figure 1). In the past, the malignant nature of this cancer had been disputed or gone unrecognized. In earlier literature, it was classified as an “acinic cell tumor” or benign “adttenoma”. Recent literature detailing the high potential for recurrence, metastases and even death resulted in WHO retclassification as a “malignant carcinoma”, though with a more common lowtgrade behavior.3

EpidemiologySalivary gland cancers comprise about 0.6% of all cantt

Acinic cell carcinoma of the salivary glands: a literature review Nabil Al-Zaher,a Amani Obeid,a Suhail Al-Salam,b Bassam Sulaiman Al-Kayyalic

From the aDepartment of Otolaryngology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia, bFRCPath, University of the United Arab Emirates, Al Ain, United Arab Emirates, and cTawam Johns Hopkins Hospital, Al Ain, United Arab Emirates

Correspondence: Nabil Al-Zaher, MD · Department of Otolaryngology, King Faisal Specialist Hospital and Research Centre · PO Box 3354, Riyadh 11211, Saudi Arabia · T: +966-1-442-3937 F: +966-1-442-3941 · [email protected] · Accepted for publication February 2009

Hematol Oncol Stem Cel Ther 2009; 2(1): 259-264

Acinic cell carcinoma (ACC) is a low-grade malignant salivary neoplasm that constitutes approximately 17% of primary salivary gland malignancies. In the head and neck region, the parotid gland is the pre--dominant site of origin and women are usually more frequently diagnosed than men. Previous radiation exposure and familial predisposition are some of the risk factors for ACC. A slowly enlarging mass lesion in the tail of the parotid gland is the most frequent presentation. The diagnosis is usually confirmed with a fine needle aspiration biopsy, and surgical excision is the main treatment of this malignant neoplasm. Other treatment modalities such as radiotherapy may be indicated in some cases. ACC has a significant tendency to recur, to produce metastases (cervical lymph nodes and lungs), and may have an aggressive evolution. Therefore, long-term follow-up is mandatory after treatment.

cers. ACCs constitute approximately 6% to 8% of all salivary gland neoplasms, and 17% of primary salivary gland malignancies, representing the third most comttmon epithelial malignancy of the salivary glands in adults, following mucoepidermoid carcinoma and adettnoid cystic carcinoma. In the pediatric age group, ACC is the second most common epithelial malignancy folttlowing mucoepidermoid carcinoma.

Women are more frequently diagnosed (58.8%) than men (41.2%).4,5 The median age at diagnosis is 52 years, younger than for most other salivary gland cancers. Slightly more than 16% of patients were unttder the age of 30 and women comprise a significantly larger proportion of cases in this younger age group (64.4%) than among those 30 years of age or older.4,5

According to the National Cancer Data Base Report on cancer of the head and neck in the United States, the parotid gland was the predominant site of origin (86.3%) for reported ACCs.4 The median tumor size was 2 centimeters and slightly more than twotthirds of cases presented for treatment during the first stage of the disease. Regional and distant metastasis, high grade, and large tumor size were all more common among patients older than 30. No ethnic or racial predilection showed an association with ACC.4, 5

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Hematol Oncol Stem Cell Ther 2(1) First Quarter 2009 hemoncstem.edmgr.com260

LocalizationBetween 81% and 98% of ACCs of the salivary glands occur in the parotid, 11% in the submandibular gland, and 3% to 12% in the minor salivary glands, most comttmonly in the palate.6 Less than 1% of ACC arise in the sublingual gland. In addition to major salivary glands, ACC of the head and neck region was reported to octtcur in the minor salivary glands,7 oral cavity,8 lips,9 palttate,10 larynx,11 mandible,12 nose13 and paranasal sinuses.14 Other sites of origin of ACC in the human body include the pancreas,15 stomach,16 lung,17 breast,18 and prostate.19

Risk factorsPossible causes of ACC include previous radiation exttposure20 and familial predisposition.21, 22 Women are more apt to get this malignant neoplasm.4,5 The authors of this article recently noticed a chronological associatttion between onset and recurrence of ACC and pregttnancy, in one case.

Longtterm followtup studies of the survivors of the atomic bomb explosions in Hiroshima and Nagasaki show an increased relative risk of 3.5 for benign and 11 for malignant salivary neoplasms. Therapeutic rattdiation, particularly of the head and neck region, has been linked with a significantly increased risk of dettveloping salivary gland cancers. There appears to be a risk from iodine 131 used in the treatment of thyroid disease, as the isotope is also concentrated in the salittvary glands. Workers in a variety of industries have an increased incidence of salivary gland carcinomas in

general. These industries include asbestos and rubber manufacturing, exposure to metal in the plumbing industry and nickel compounds, woodworking in the automobile industry and employment in hairdressing and beauty shops.1

A number of viruses have been implicated in the pathogenesis of salivary gland tumors. There is a strong association between Epstein Barr Virus (EBV) and lymphoepithelial carcinomas, but EBV has not been shown in ACC or other salivary gland carcinomas.1

Endogenous hormones have been reported in norttmal and neoplastic salivary glands, but some of the rettsults have been conflicting. Estrogen receptors have been reported in a minority of cases of ACC, mucoepidermoid carcinoma, and salivary duct carcinoma.1 Progesterone receptors and androgen receptors were also seen in some cases of ACC. These findings raised suspicion that some of the salivary gland neoplasms including ACC might be hormonally dependent like breast carcinoma.1

Clinical presentationParotid ACC typically presents with a slowly enlarging mass in the parotid region. Spiro et al found out that 34.3% to 50.8% were palpated in the tail of the parotid gland.23 Pain (7.5%) and facial nerve palsy (3.0%) were seldom reported. Most of the previously untreated patttients had been aware of the lesion for less than one year and in about 7%, intervals of 5 to 10 years elapsed bettfore a physician was consulted.23

Presentation with lymph node or distant metastasis occurs rarely. At least one case was reported where a patient presented with a lymph node metastasis high in the jugular chain of nodes, without a palpable abttnormality of the ipsilateral parotid gland. Distant lung metastasis have been reported to occur as the presenttting finding from occult parotid primary ACC, which despite extensive clinical evaluation, only became apttparent 1 year after initial diagnosis.24 Bilateral occurttrence,21 familial cases,21, 22 and presentation in children have also reported.25

Recurrence and metastasisACC has a significant tendency to recur, to produce metttastases (cervical lymph nodes and lungs), and may have an aggressive evolution.26 The average recurrence rate among several studies is estimated to be around 35%.1,4,5 Late local recurrence was reported in many cases, up to 30 years from the initial presentation.4,5,27 Metastases tend to be hematogenous rather than lymphatic, with a propensity for lung and bone. Distant spread occurs in 12% of all patients during the course of ACC. Most common sites are cervical lymph nodes (16% of ACC

Figure 1. Acinic cell carcinoma, which is encapsulated (arrow), and consists of clusters of malignant cells forming acini (left). The malignant cells themselves are pleomorphic and have atypical nuclei (hematoxylin and eosin, 40×). (Courtesy of Dr. H. El Teraifi)

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patients) and the lungs.4,5,23,26,28 Other reported sites include the cavernous sinus, spine, sternum, orbit, and the liver and skin. Moreover, intracranial extension of parotid ACC has been mentioned in the literature.29t33

Pathogenesis and pathologyRelatively large studies to identify the submicroscopic changes associated with the development and progresttsion of salivary gland tumors have recently been conttducted. The genetic alterations linked to ACC of the parotid gland included alterations at chromosomes 4p, 5q, 6p, and 17p, suggesting the association of tumor suppressor genes with the oncogenesis of these tumors. Moreover, deletions of chromosome 6q, loss of Y and trisomy 21 have been reported in association with ACC.34,35 Further molecular studies indicated that retittnoblastoma pathways, which are common to most huttman tumors, might also be involved in the pathogenesis and etiology of ACC.36

Acinic/acinar/acinous cell carcinoma belongs to the family of adenocarcinomas. Cancers with some similarities include adenoid cystic, mucotepidermoid, lowtgrade adenocarcinomas, and possibly some breast cancers. Secretory carcinoma of the breast may be an identical entity.3

HistologyUntreated ACCs usually present as solitary, encapsulated, soft tumors of a greytwhite color (Figure 1). In recurrent lesions, the tumor often appears lobulated, the capsule may be absent, and areas of necrosis may be evident.23

ACC is histologically defined by serous acinar cell difttferentiation (Figure 2). However, several cell types and histomorphologic growth patterns are recognized. These include acinar, intercalated ductal, vacuolated, clear, and nontspecific glandular and solidtlobular, microcystic, papillarytcystic, and follicular growth patterns.23,37t43

The majority of tumor cells in ACC were described as having many ultrastructural features similar to those found in the normal serous acinar cells. These cells were round or polygonal with eccentrically placed nuclei and inconspicuous nucleoli. The lightly basottphilic cytoplasm was usually finely or coarsely granuttlar, but was clear focally in some cases. Occasionally, this clear, vacuolated cytoplasmic pattern was evident throughout the entire tumor. Numerous intercellular microcysts, cysts, crude acini, glandtlike areas and large papillary cystic spaces have been described in some cases, and well developed glandular configuratttions occur rarely. Regardless of the cell pattern, apttpropriate sections often revealed microscopic invasion of the capsule and even nests of tumor cells outside of

the capsule.2,23,44 Calcification may be prominent. Drut and Gimenez reported ACC of the salivary gland with massive deposits of globular amyloid.45

Attempts at histological grading have been controttversial and inconsistent. Features that are often associttated with more aggressive tumors include frequent mitttoses, focal necrosis, neural invasion, pleomorphism, infiltration, and stromal hyalinization. Occasional cases of dedifferentiation from a lowtgrade to a hightgrade malignancy have been reported. These tumors are characterized by cytological pleomorphism, inttcreased mitotic and proliferation indices and have a worse prognosis.1

DiagnosisThe diagnosis of ACCs frequently presents difficulttties, owing to its great radiological46,47 and cytological similarity with benign tumors and with normal acinar component of the salivary gland, respectively. The difttferential diagnosis is considered, fundamentally, with clear cell carcinomas, mucoepidermoid carcinomas, Warthin’s tumor, and oncocytomas.2,23,44

Fine Needle Aspiration Biopsy (FNAB)FNAB has been well established in the diagnosis of salivary gland lesions as it provides essential informatttion on the diagnostic/therapeutic management of these tumors; this methodology is highly sensitive in its diagnostic efficacy. The cytologic findings in finet

Figure 2. Acinic cell carcinoma cells growing in a solid pattern. most of the tumor cells demonstrate fine serous cytoplasmic granules, resembling the normal serous acinar salivary gland cells. Some tumor cells with a clear cytoplasm are also noted (H&E stain, original magnification 400×). (Courtesy of Dr. A. Al Mutawa)



needle aspiration (FNA) biopsies of ACCs are usually characterized by acinar differentiated tumor cells and by certain cytoarchitectural patterns.46,47 ACC is a comttmon cause of false negative interpretation owing to the conspicuous absence of hallmark morphologic features of malignancy such as necrosis, cellular pleomorphism, and high mitotic activity. It is frequently mistaken for benign salivary gland tumors (e.g. oncocytoma) and even nontneoplastic parotid parenchyma.47

Radiological StudiesIn addition to FNAC and other ancillary diagnostic tests, imaging studies are usually used in the pretreatttment assessment and management planning of ACC which might include ultrasonography, CT, MRI, and nuclear scans. Ultrasonography, which is an easy, nontinvasive, and widely available test method, is useful in evaluating tumor size, location, and the nature of the tuttmor. In addition, it is also used to perform ultrasoundtguided FNA biopsies. A CT scan usually demonstrates slight contrast enhancement and may be necessary for evaluation of tumor size, extension, relationship to fattcial nerve and other structures, and distant metastasis (Figure 3).

ACC usually demonstrates a nonspecific signal intensity pattern on MRI scan that can occasionally be somewhat similar to the signal produced by some benign salivary neoplasms. Low T1 and T2 signals can be detected on some images. The signals correlate

with the histology, suggesting vascularity, haemosidtterin deposition, fibrosis and calcification within the tumor itself.48,49

ManagementIn general, management of ACC consists of complete surgical removal of the tumor, by total or subtotal pattrotidectomy. Postoperative radiotherapy may be useful for recurrent, undifferentiated cases of ACC, positive margins, and advanced tumors with cervical lymph node spread.4,5,38,50 A total parotidectomy with removal of the facial nerve might be necessary for some of the T3 and T4 cases, and neck dissection may also be inttdicated. Nerve grafting after total nerve resection is recommended for a better quality of life.51,52 Cervical lymphadenectomy was reported for 12.1% of cases. Nodes were confirmed as positive in 36.6% of patients who underwent neck dissection.

Incomplete excision is associated with a lower chance of survival so if complete and total tumor removal is not achievable, radiation should always be considered. Over the past three decades, radiation treatment alone, spettcifically with fast neutron beam radiation, has shown promising and effective results, especially for inoperable tumors. That means that it is a viable alternative to surttgery, not just a postoperative adjunct.53 North et al conttcluded that radiotherapy is recommended for all cases of salivary gland cancer postoperatively except for those tumors staged as T1N0 or T2N0 with lowtgrade histttology, which were excised with negative margins. It is the opinion of the Acinic Cell Carcinoma Information Centre at this time, that these are reasonable criteria and that fast neutron beam radiation should be strongly considered either instead of surgery, or posttoperatively, in all the above described cases.3

Weighing all the pros and cons, the Acinic Cell Carcinoma Information Centre currently recommends that fast neutrons are the first “treatment of choice” to consider in most ACC cases and that this treatment provides the best chance for longtterm local control of disease. This is especially the case for inoperable or unttresectable tumors, incomplete tumor removal, residual disease, and recurrences. Unfortunately, there are a very limited number of high energy fast neutron treatment centers worldwide, which sometimes provides a logistittcal challenge. If fast neutron treatment is not an option for the patient, accelerated hyperfractionated dosing of conventional beams should be considered. This method has also resulted in high rates of longtterm locotregionttal controls in salivary gland cancers.3,54t56

Chemotherapy for ACC has largely been considered ineffective, except for paintrelief or partial responses.

Figure 3. An axial CT-scan image of a solid mass lesion (acinic cell carcinoma) within the right parotid gland (Courtesy of Dr. N. Al Zaher).

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The use of chemotherapy for malignant salivary gland tumors in general remains under evaluation. ACC has been considered chemotresistant, which is likely due to the (usually) slow metabolism of this cancer.3

Predictive Factors and PrognosisACC of the salivary glands are distinctive neoplasms of individually unpredictable behavior. Contrary to the widely accepted notion that ACCs can be equated with favorable prognostic groups, such as lowtgrade mucoepittdermoid carcinoma or low grade adenocarinomas, recent studies are increasingly suggesting that there is a subset of ACCs with poor prognosis. Prolonged followtup data are believed necessary to gauge the impact of treatment on survival. Aggressive tumors were treated three times as frequently with surgery and radiation compared with treatment patterns for less aggressive disease.4,5

Muliple recurrences and metastasis to cervical lymph nodes indicate a poor prognosis. Distant metastasis is associated with very poor survival. While tumors in the submandibular gland are more aggressive than those in the parotid gland, ACCs in minor salivary glands are less aggressive than those in the major salivary glands.1

The overall 5tyear diseasetspecific survival is estimattted to be around 91%, and 88% at 10 years. Significant

association was noted between poor survival and hightgrade disease, regional or distant metastasis at presentttation, submandibular tumors, pain, male gender, and age older than 30 years.57 Short duration of symptoms, incomplete excision, frequent mitoses, focal necrosis, pleomorphism, neural invasion, infiltration, stromal hyalinization, large size and involvement of the deep lobe of the parotid gland have also been reported as poor prognostic factors.58 In other studies, the presence of a predominately solid architecture was strongly assottciated with a poor outcome.49,59 For hightgrade tumors, the 5tyear survival rate was only 33%.6

SurveillanceAlthough indolent in nature (slowtgrowing), ACCs are quite persistent in their potential for local recurrences and distant metastases, often many years later. Local and multiple recurrences may occur in up to half of patttients. Recurrences and metastases after 3 to 10 years are common, especially after inadequate primary tumor removal. Recurrences more than 20 or 30 years after initial treatment are also noted in the literature.3 Due to the notably high tendency of ACC to recur and to produce latent metastasis, longtterm followtup is manttdatory after treatment.4t6,26, 27

1. Barnes L, Eveson JW, reichart P, Sidransky D. World Health Organization Classification of Tu--mours. Pathology and Genetics of Head and Neck Tumours. IArC Press: Lyon; 2005.2. Godwin JT, Foot FW Jr, Frazell EL. Acinic cell adenocarcinoma of the parotid gland: report of twenty-seven cases. Am J Pathol. 1954; (30):465-477.3. Acinic Cell Carcinoma Overview, Acinic Cell Carcinoma Information Centre. [homepage on the Internet] [updated 2005 July 16; cited 2008 Sep 23]. Available from: http://www.aciniccell.org/over--view.html4. Hoffman HT, Karnell LH, robinson rA, Pinkston JA, menck Hr. National Cancer Data Base report on cancer of the head and neck: Acinic Cell Carci--noma. Head and Neck. 1999 Jul; 21(4):297-309.5. Stewart AK, Bland KI, mcGinnis LS, morrow m, Eyre HJ. Clinical Highlights from the National Can--cer Data Base. CA Cancer J Clin. 2000; (50):171-183.6. Federspil PA, Constantinidis J, Karapantzos I, Pahl S, markmann HU, Iro H. Acinic cell carcino--mas of the parotid gland. A retrospective analysis. HNO. 2001 Oct; 49(10):825-830.7. Chou C, Zhu G, Luo m, Xue G. Carcinoma of the minor salivary glands: results of surgery and combined therapy. J Oral maxillofac Surg. 1996 Apr;54(4):448-453.8. Keane Wm, Denneny JC 3rd, Atkins JP Jr, mc--Brearty F. Acinic cell carcinoma of the oral cav--ity. Otolaryngol Head Neck Surg. 1982 Nov-Dec; 90(6):696-699.9. mocan S, Stolnicu S, r_dulescu D, Petrovan C. Acinic cell adenocarcinoma of the lip. rev med Chir Soc med Nat Iasi. 2005 Jan-mar; 109(1):164-

169.10. Utsunomiya T, Yamamoto H, Kuyama K, Itami m, Asanuma K. Acinic Cell Carcinoma of the Pal--ate: Case report and Immunohistochemical Ob--servation. Arch Otolaryngol Head Neck Surg. 1999 Sep; (125):1025-1028.11. Boscolo-rizzo P, da mosto mC, marchiori C, Boccato P. Transglottic acinic cell carcinoma. Case report and literature review. OrL J Otorhino--laryngol relat Spec. 2004; 66(5):286-289.12. Hara I, Ozeki S, Okamura K, Toshitani K, Tanigu--chi K, Honda T, Ohishi m. Central acinic cell carci--noma of the mandible. Case report. J Craniomaxil--lofac Surg. 2003 Dec; 31(6):378-382.13. von Biberstein SE, Spiro JD, mancoll W. Acinic cell carcinoma of the nasal cavity. Otolaryngol Head Neck Surg. 1999 may; 120(5):759-762.14. manace ED, Goldman JL. Acinic cell carcino--ma of the paranasal sinuses. Laryngoscope 1971; (81):1074-1082.15. Kitagami H, Kondo S, Hirano S, Kawakami H, Egawa S, Tanaka m. Acinar cell carcinoma of the pancreas: clinical analysis of 115 patients from Pancreatic Cancer registry of Japan Pancreas Society. Pancreas. 2007 Jul; 35(1):42-46.16. Sun Y, Wasserman PG. Acinar cell carcinoma arising in the stomach: a case report with litera--ture review. Hum Pathol. 2004 Feb ;35(2):263-265.17. Ukoha OO, Quartararo P, Carter D, Kashgar--ian m, Ponn rB. Acinic cell carcinoma of the lung with metastasis to lymph nodes. Chest. 1999 Feb; 115(2):591-595.18. Tanahashi C, Yabuki S, Akamine N, Yatabe Y, Ichihara S. Pathol Pure acinic cell carcinoma of the breast in an 80-year-old Japanese woman. Int. 2007 Jan; 57(1):43-6.

19. Luebke Am, Schlomm T, Gunawan B, Bonkhoff H, Füzesi L, Erbersdobler A. Simultaneous tumour-like, atypical basal cell hyperplasia and acinar adenocarcinoma of the prostate: a comparative morphological and genetic approach. Virchows Arch. 2005 mar; 446(3):338-341.20. Squires JE, mills SE, Cooper PH, Innes DJ Jr, mcLean WC. Acinic cell carcinoma: its oc--currence in the laryngotracheal junction after thyroid radiation. Arch Pathol Lab med 1981 may; 105(5):266-268.21. Betkowski A, Cyran-rymarz A, Domka W. Bi--lateral acinar cell carcinoma of the parotid gland. Otolaryngol Pol. 1998; 52(1):101-104.22. Delides A, Velegrakis G, Kontogeorgos G, Kara--gianni E, Nakas D, Helidonis E. Familial bilateral acinic cell carcinoma of the parotid synchronous with pituitary adenoma: case report. Head Neck. 2005 Sep;27(9): 825-828.23. Spiro rH, Huvos AG, Strong EW. Acinic cell carcinoma of salivary origin: A Clinicopathologic Study of 67 Cases. Cancer. 1978; (41):924-935.24. Tavora F, rassaei N, Shilo K, Foss rD, Galvin Jr, Travis WD, Franks TJ. Occult primary parotid gland acinic cell adenocarcinoma presenting with extensive lung metastasis. Arch Pathol Lab med. 2007 Jun; 131(6):970-973.25. Sato T, Kamata SE, Kawabata K, Nigauri T, mi--tani H, Beppu T, Sato m. Acinic cell carcinoma of the parotid gland in a child. Pediatr Surg Int. 2005 may; 21(5):377-380.26. Zbären P, Schreiber B, Lehmann W, Widgren S. Acinar cell carcinoma of the salivary glands. Lar--yngol rhinol Otol (Stuttg). 1987 Jun; 66(6):320-323.27. miki H, masuda E, Ohata S, Komaki K, Hirokawa m, Uehara H, Asano H, monden Y. Late recurrence

REFERENCES



of acinic cell carcinoma of the parotid gland. J med Invest. 1999 Aug; 46(3-4):213-216.28. H, miyasaka S, Kanaoka Y, Tanaka Y, Horio H, mori T. A case of metastatic lung tumor from acinic cell tumor of the parotid gland. Nakamura Nippon Kyobu Geka Gakkai Zasshi. 1994 Oct; 42(10):1960-1962.29. Yildirim N, Oksüzo_lu B, Vural m, Han O, Zengin N. Case report: cavernous sinus metastasis of the parotid carcinoma: a very unusual case. Journal of Neuro-Oncology. 2005; (73):181-183.30. Vidyadhara S, Shetty AP, rajasekaran S. Wide--spread metastases from acinic cell carcinoma of parotid gland. Singapore med J. 2007 Jan; 48(1):e13-15.31. Smukalla K, Kalinski T, motsch C. Distant me--tastases on Acinic Cell Carcinoma of the Parotid Gland after 12 Years Symptom-free Interval. Laryn--gorhinootologie. 2006; (85): 586-588.32. Varsegi mF, ravis Sm, Hattab Em, Henley JD, Billings SD. Widespread cutaneous metastases from acinic cell carcinoma 20 years after primary presentation. J Cutan Pathol 2008 Jun; 35(6):591-593.33. Spencer mL, Neto AG, Fuller GN, Luna mA. Intracranial extension of acinic cell carcinoma of the parotid gland. Arch Pathol Lab med. 2005 Jun; 129(6):780-282.34. el-Naggar AK, Abdul-Karim FW, Hurr K, Callen--der D, Luna mA, Batsakis JG. Genetic alterations in acinic cell carcinoma of the parotid gland de--termined by microsatellite analysis. Cancer Genet Cytogenet. 1998 Apr 1; 102(1):19-24.35. Sandros J, mark J, Happonen rP, Stenman G. Specificity of 6q- markers and other recurrent de--viations in human malignant salivary gland tumors. Anticancer res.1988; (8): 637-643.36. Liu T, Zhu E, Wang L, Okada T, Yamaguchi A, Okada N. Abnormal expression of rb pathway-re--lated proteins in salivary gland acinic cell carci--noma. Hum Pathol. 2005 Sep; 36(9):962-970.37. Batsakis JG, Luna mA, El Naggar AK. Histo--pathologic grading of salivary gland neoplasms: II.

Acinic cell carcinomas. Ann Otol rhinol Laryngol. 1990; (99): 929-933.38. Colmenero C, Patron m, Sierra I. Acinic cell carcinoma of the salivary glands. A review of 20 new cases. J Craniomaxillofac Surg 1991;(19): 260-266.39. Ellis GL, Auclair PL. Tumours of the salivary glands. 3rd ed. Armed Forces Institute of Pathol--ogy: Washington; 1996.40. Lewis JE, Olsen KD, Weiland LH. Acinic cell carcinoma. Clinico-pathologic review. Cancer 1991; (67): 172-179.41. Shet T, Ghodke r, Kane S, Chinoy rN. Cyto--morphologic patterns in papillary cystic variant of acinic cell carcinoma of the salivary gland. Acta Cytol. 2006 Jul-Aug; 50(4):388-392. 42. Seifert G. Histopathology of malignant salivary gland tumors. Eur J Cancer B Oral Oncol 1992; (28B):49-56. 43. Seifert G, Sobin LH. Histological Typing of Salivary Gland Tumours. 2nd ed. Springer-Verlag: Berlin; 1996.44. Echevarria rA. Ultrastructure of the acinic cell carcinoma and clear cell carcinoma of the parotid gland. Cancer 1967; (20): 563-571.45. Drut r, Giménez PO. Acinic cell carcinoma of salivary gland with massive deposits of globular amyloid. Int J Surg Pathol 2008 Apr; 16(2):202-207.46. Nagel H, Laskawi r, Büter JJ, Schröder m, Chilla r, Droese m. Cytologic Diagnosis of Acinic-Cell Carcinoma of Salivary Glands. Diagn Cytopa--thol: 1997 may; 16(5):402-412.47. Alphs HH, Eisele DW, Westra DH. The role of fine needle aspiration in the evaluation of parotid masses. Current Opinion in Otolaryngology and Head and Neck Surgery. 2006 April; 14(2):62-66.48. Som Pm, Bergeron rT. Salivary glands. Head and neck imaging. mosby Year Book, St.Louis; 1991: 277-348.49. Sakai O., Nakashima N., Takata Y., Furuse m. Acinic cell carcinoma of the parotid gland: CT and mrI. Neuroradiology 1996; (38): 675-679.50. Kane WJ, mcCaffrey TV, Olsen KD, Lewis

JE. Primary parotid malignancies. A clinical and pathologic review. Arch Otolaryngol Head Neck Surg 1991 mar; 117(3):307-315.51. Kim SA, mathog rH. Acinic cell carcinoma of the parotid gland: a 15-year review limited to a single surgeon at a single institution. Ear Nose Throat J. 2005 Sep; 84(9):597-602.52. Sakamoto K, Chijiwa H, miyajima Y, Umeno H, Nakashima T. A retrospective study of malignant parotid tumors. Nippon Jibiinkoka Gakkai Kaiho. 2006 Feb; 109(2):103-111.53. Laramore GE. Fast neutron radiotherapy for in--operable salivary gland tumors: is it the treatment of choice? Int J radiat Oncol Biol Phys 1987 Sep; 13(9):1421-1423.54. Buchholz TA, Laramore GE, Griffin Br, Koh WJ, Griffin TW. The role of fast neutron radiation therapy in the management of advanced salivary gland malignant neoplasms. Cancer 1992 Jun; 69(11):2779-2788.55. Douglas JG, Lee S, Laramore GE, Austin-Sey--mour m, Koh W, Griffin TW. Neutron radiotherapy for the treatment of locally advanced major salivary gland tumors. Head Neck. 1999 may; 21(3):255-263.56. Leborgne F, Zubizarreta E, Fowler J, Ortega B, mezzera J, Deus JL, Leborgne JH. Improved results with accelerated hyperfractionated radio--therapy of advanced head and neck cancer. Int J Cancer 2000 Apr 20; 90(2):80-91.57. Wahlberg P, Anderson H, Biorklund A, moller T, Perfekt r. Carcinoma of the parotid and subman--dibular glands-a study of survival in 2465 patients. Oral Oncol 2002 Oct; 38(7):706-713.58. The Doctor’s Doctor.com page on Acinic Cell Carcinoma. [home page on the Internet] [updated Last Updated 2008 June 19; cited 2009 Feb 28] Available from: http://www.thedoctorsdoctor.com/diseases/aciniccell_ca.htm59. Timon CI, Dardick I, Panzarella T, Thomas J, El--lis G, Gullane P. Clinico-pathological predictors of recurrence for acinic cell carcinoma. Clin Otolar--yngol Allied Sci. 1995 Oct; 20(5):396-401.

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Acinic Cell Carcinoma